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Glutathione metabolism in cobalamin deficiency type C (cblC)
Author(s) -
Pastore Anna,
Martinelli Diego,
Piemonte Fiorella,
Tozzi Giulia,
Boenzi Sara,
Di Giovamberardino Gianna,
Petrillo Sara,
Bertini Enrico,
DionisiVici Carlo
Publication year - 2014
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-013-9605-3
Subject(s) - glutathione , methylmalonic aciduria , cobalamin , homocystinuria , cysteine , homocysteine , oxidative stress , methylmalonic acid , biochemistry , glutathione synthetase , glutathione disulfide , biology , medicine , chemistry , vitamin b12 , methionine , amino acid , enzyme
Background Methylmalonic aciduria with homocystinuria, cblC defect, is the most frequent disorder of vitamin B 12 metabolism. CblC patients are commonly treated with a multidrug therapy to reduce metabolite accumulation and to increase deficient substrates. However the long‐term outcome is often unsatisfactory especially in patients with early onset, with frequent progression of neurological and ocular impairment. Recent studies, have shown perturbation of cellular redox status in cblC. To evaluate the potential contribution of oxidative stress into the patophysiology of cblC defect, we have analyzed the in vivo glutathione metabolism in a large series of cblC deficient individuals. Methods Levels of different forms of glutathione were measured in lymphocytes obtained from 18 cblC patients and compared with age‐matched controls. Furthermore, we also analyzed plasma cysteine and total homocysteine. Results We found an imbalance of glutathione metabolism in cblC patients with a significant decrease of total and reduced glutathione, along with a significant increase of different oxidized glutathione forms. Conclusions These findings show a relevant in vivo disturbance of glutathione metabolism underlining the contribution of glutathione pool depletion to the redox imbalance in treated cblC patients. Our study may be helpful in addressing future research to better understanding the pathogenetic mechanism of the disease and in developing new therapeutic approaches, including the use of novel vitamin B 12 derivatives.